Piriformis syndrome--an attempt to understand its pathology.

OBJECTIVE: Gross anatomy of the hip rotators and histology of the sciatic nerves in adult cadavers were studied, aiming to the identification of possible pathologic changes related to the piriformis syndrome (PS). MATERIAL: 50 cadavers were dissected; in 17 cases with macroscopical findings the sciatic nerves were harvested (34 sciatic nerves; 17 cadavers). History of low back or leg pain was not available. METHOD: Site anatomy and additional findings at the harvesting sites were recorded, such as anatomical variations, adhesions, hematomas etc. All nerves were additionally microscopically analyzed. In cases with findings at the dissection, the contralateral unaffected nerves served as controls. All the dissected nerves were conserved in 10% formalin solution, embedded in paraffin, stained with Hematoxylin and Eosin (H&E) and immunolabeled with antibodies against Neurofilament (NF). RESULTS: Both the H&E staining as well as the performed immunohistochemistry showed, to a variable degree, significant alterations in the structure of the affected nerves compared to the controls. CONCLUSIONS: These findings both in the local anatomy and sciatic nerve correspond to lesions that are expected in PS. Nevertheless, since this was a cadaveric study, unassociated to a certain pain patient's history, results should be considered and interpreted as an indication of a sciatic nerve injury in PS.

Microvessel density (MVD) and cyclooxygenase-2 (COX-2)/ beta-catenin interaction are associated with relapse in patients with transitional carcinoma receiving adjuvant chemotherapy with paclitaxel/carboplatin: a hellenic cooperative oncology group (HECOG) study.

BACKGROUND: Cycloxygenase (COX)-2 has been associated with proliferation, apoptosis and angiogenesis in urothelial cancer. The prognostic significance of COX-2 in patients who received adjuvant chemotherapy for urothelial cancer was examined. PATIENTS AND METHODS: Expression of COX-2, p53, ki67, beta-catenin, vascular endothelial growth factor (VEGF) and microvessel density (MVD) were studied retrospectively in 59 patients with urothelial cancer (pT3, pT4, N+) who had undergone surgery. The patients had subsequently received adjuvant chemotherapy. RESULTS: Thirty-eight out of 59 cases (64%) were positive for COX-2. COX-2 was not associated either with progression-free survival (PFS) or overall survival (OS). MVD levels > or =47 were associated with longer median PFS compared with lower levels (not reached vs. 13 months [95% CI: 8-18], p=0.048). The median PFS for patients with beta-catenin nuclear accumulation and COX-2 expression was 6 months (95% CI: 4-7) compared with 19 months (95% CI: 14-23) for neither or only one of these factors (p=0.018). CONCLUSION: MVD may be a useful indicator of relapse in high-risk urothelial cancer treated with adjuvant chemotherapy.

Extracellular regulated kinase-2 immunoreactivity increases in parallel with cervical intraepithelial neoplasia grade in cervical neoplasia.

The cell cycle control system includes cyclins, cyclin-dependent kinases (CDK), and their inhibitors (CDK1). Extracellular regulated kinase (ERK1/2) (p44 and p42 mitogen-activated protein kinases [MAPKs]) is a component of the MAPK pathway, which is associated with cyclin D1 and CDK. It is a critical signaling system for the induction of cell proliferation, differentiation, and cell survival. The aim of this study was to investigate the usefulness of ERK2 expression as a marker of biological aggressiveness complementary to cervical intraepithelial neoplasia (CIN) grade as well as to compare its expression in preinvasive lesions with that in invasive carcinoma. Paraffin-embedded sections of 146 CIN lesions (32 CIN I, 49 CIN II, and 43 CIN III) and 22 invasive cervical carcinomas (13 squamous and 9 adenocarcinomas) were used for the standard immunohistochemical procedure with the application of the ERK2 monoclonal antibody. ERK2 staining displayed a cytoplasmic and nuclear pattern. The staining intensity was gradually increased according to the severity of the dysplastic lesions; ERK2 immunoreactivity was significantly increased in high-grade dysplastic lesions (CIN II and CIN III) and invasive carcinomas by comparison to low-grade dysplastic lesions (CIN I) (P < 0.001). When high-grade lesions were separately assessed, the differences between each one of them and CIN I retained their statistical significance: CIN II versus CIN I (P < 0.001) and CIN III versus CIN I (P < 0.001). In conclusion, our study found a direct relationship between the increasing grade of the dysplastic cervical lesions and the intensity of ERK2 staining, thus implying a role of ERK2 as an early event in cervical carcinogenesis.

Tissue detection of natural killer cells in laryngeal carcinoma.

Natural Killer (NK) cells have gained much attention as potential cells in antitumor immune defense mechanisms. In a group of 31 patients with surgically treated squamous cell laryngeal carcinoma, NK cell presence was semiquantitatively assessed by means of immunohistochemistry. A panel of three monoclonal antibodies including anti-CD16, was applied on frozen tissue sections. High CD 16+ cell presence was more frequently detected in poorly differentiated carcinomas (in 6 out of 14 cases) by comparison to carcinomas of high to moderate degrees of differentiation (in 1 out of 16 cases, p=0.031). No other clinicopathological variable appeared to influence NK cell presence in the examined specimens. No relation between NK cell detection and relapse-free survival emerged. Poorly differentiated laryngeal cancer cells appear to trigger off a greater NK cell tissue response than well and moderately differentiated cancer cells; however, the potential prognostic impact of this observation remains to be established.

Topoisomerase I protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy.

PURPOSE: Our aim was to investigate whether chemotherapy with 5-FU induces an alteration in the levels of topoisomerase I (topo I) in colorectal neoplastic tissues METHODS: Twenty-five colorectal cancer patients were included in our study; these had undergone surgical resection of the primary tumor, received post-operatively 5-FU-based adjuvant chemotherapy and then suffered from recurrences. In a standard three-step immunohistochemical procedure, a monoclonal antibody to topo I was applied in both specimens from each patient (one from the primary location and a second one from the recurrence). Statistical analysis was subsequently performed. RESULTS: Malignant cells from the recurrences displayed a statistical significant increase, concerning the levels of topoisomerase I, by comparison with the primary tumors (P=0.01). The increase in topo I levels did not demonstrate significant correlations with Duke's stage (Fisher's Exact Test P value=0.496), differentiation grade (P value=0.661), localization (P value=0.072), patient sex (P value=0.434), nor with relapse free interval (P value=0.493). There was a statistically significant relationship between the age of patients and increase in topo I levels (P=0.011). CONCLUSIONS: Topo I expression may be part of the malignant cells' phenotype in recurrent colorectal carcinomas, suggesting a potential role for Topo I in the acquisition of a metastatic phenotype. The increase of topo I immunohistochemical status is likely to be attributed to 5-FU and given the fact that high levels of topo I correlate with sensitivity to camptothecin, advanced colorectal cancer patients seem to benefit from topo I targeted anticancer drug therapy.

Tissue evaluation of immune markers in endometrial and cervical carcinomas.

Major histocompatibility complex (HLA system) class II molecules including HLA-DR antigens, associate with peptides, which are derived from antigens, for presentation to T4 lymphocytes. Functional and adhesion assays have shown that CD4 molecule interacts with HLA class II molecules, leading to enhanced responses of T4 cells. In the present study, we examined the tissue expression of HLA-DR antigens and the quantitative variance of T4 lymphocytes in a series of 50 "endometrioid" adenocarcinomas of the endometrium and 35 cervical squamous-cell carcinomas. A three-step avidin-biotin immunoperoxidase staining method was applied. As primary antibodies, we used the TAL.1BS monoclonal antihuman HLA-DR alpha (alpha) chain antibody and the OPD4 mouse antihuman antibody; the latter mainly identifies benign T4 lymphocytes. Twenty-four percent (24%) of women with endometrial cancer were high immune responders, while the relative percentage in women with cervical cancer was 40%; the respective tumours were of early clinical and surgical stages. HLA-DR determinants were predominantly expressed in membranes of stromal cells, mainly histiocytes, usually around HLA-DR+ lymphoid cells, as well as on endothelial cells. Greater numbers of OPD4+ aggregated lymphocytes were observed when the tumour stroma was rich in HLA-DR+ cells. Epithelial elements, either cancerous or benign, were seldom HLA-DR+. In those samples, positive immunolabelling was often confined in the intercellular space and did not seem to activate an effective host immune response against neoplastic cells. High expression of HLA-DR molecules in professional antigen presenting stromal cells may be used as a lymphocyte activation marker in endometrial and cervical carcinomas. This activation appears to be an early event in the evolution of invasive endometrial and cervical carcinomas.

Detection of apoptotic cells in archival tissue from diffuse astrocytomas using a monoclonal antibody to single-stranded DNA.

Precise quantitation of apoptotic cells in gliomas is necessary to determine the role of apoptosis in tumour growth, prognosis, and treatment. This study investigated the incidence of baseline apoptosis in relation to proliferation status, p53 expression, standard clinicopathological parameters, and outcome, in a series of 61 patients with diffuse cerebral astrocytomas. Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing exposed single-stranded (ss) regions in the DNA of apoptotic cells during heating. Proliferative activity was expressed as the percentage of Ki-67-positive cells. Tissues consisted of primary formalin-fixed, paraffin-embedded astrocytoma specimens. The apoptotic index (AI) increased with grade, proliferative activity, and p53 expression. Increased AI tended to be accompanied by a shortened overall and disease-free survival in univariate analysis in glioblastoma multiforme and astrocytoma/anaplastic astrocytoma, respectively. Multivariate analysis demonstrated that increased AI was an independent predictor of adverse significance in overall and disease-free survival. These results implicate apoptotic rate in astrocytoma aggressiveness and show that the assessment of apoptotic potential by means of anti-ssDNA monoclonal antibody provides valuable prognostic information independently of standard parameters or tumour proliferation status.

Chronic anicteric intrahepatic cholestasis associated with ankylosing spondylitis. Beneficial treatment by clofibrate.

A case of anicteric idiopathic intrahepatic cholestasis in association with ankylosing spondylitis is described. No primary cause for the cholestatic syndrome was found and the liver histology was repeatedly normal. Results of treatment with clofibrate (2 g daily) were very satisfactory, as the symptoms and signs of cholestasis had gradually subsided. Discontinuation of the treatment was followed rapidly by a recurrence of the cholestasis with a new improvement after restarting treatment. The beneficial mechanism of action of clofibrate on the intrahepatic cholestasis in the case described remains speculative.